A Philly native won his second Nobel Prize in chemistry. Here’s what to know about the rare twofer.

Philadelphia native K. Barry Sharpless won his second Nobel Prize in chemistry Wednesday, a rare double honor that came 21 years after he won his first one, in 2001.

A 1959 graduate of Friends’ Central School in Wynnewood, the 81-year-old scientist is being honored for pioneering a concept called “click chemistry” — combining chemical building blocks in such an efficient way that many have likened it to assembling Lego pieces.

A longtime faculty member at Scripps Research in La Jolla, Calif., Sharpless developed one such method that is now widely used to make drugs and map DNA — a tongue-twister called copper catalyzed azide-alkyne cycloaddition. He shares the Nobel with Carolyn R. Bertozzi of Stanford University and Morten Meldal of the University of Copenhagen.

» READ MORE: Three chemists win Nobel Prize for making molecules ‘click’ to design better medicines

Sharpless won his first chemistry Nobel for his work on another type of chemical reaction used to produce drugs, called chirally catalyzed oxidation reactions.

In an afternoon news conference, he said Nobel officials woke him with the news in a phone call at 2:30 a.m. California time. Asked to describe how he devised new ways to combine chemical substances, he said it was helpful to “think like a molecule.”

“I get excited when I see something that doesn’t fit,” he said.

The only other two-time winner in chemistry was British scientist Frederick Sanger, who won in 1958 and 1980. Other two-time Nobel winners in the sciences include John Bardeen, who won twice for physics, and Marie Curie, whose two prizes came in different fields, physics and chemistry.

Seva Rostovtsev, a chemist at FMC Corp. who once worked for Sharpless at Scripps as a postdoctoral researcher, said his former boss was driven by creativity and “enormous energy.”

“In my time there, I don’t think I had a single meeting with Barry where he didn’t have half a dozen ideas of things to try,” said Rostovtsev, a Media resident and head of discovery chemistry at FMC’s Stine Research Center in Newark, Del.

Peter Schultz, chief executive officer of Scripps Research, said Sharpless’ work has had profound implications beyond drug discovery.

“His work opened whole new scientific frontiers that have had a major impact on the fields of chemistry, biology, and medicine,” Schultz said. “Barry has a remarkable combination of chemical insight, uncanny intuition, and real-world practicality — he is a chemist’s chemist and a wonderful colleague.”

In a 2019 interview with Chemical & Engineering News, Sharpless said he learned a valuable skill at Friends’ Central — learning to read and speak German, which would later come in handy when poring through old chemistry studies in that language. But beyond that, he said he spent much of his time at the Quaker school daydreaming about fishing.

“I didn’t learn much in school except what I needed to do to get A’s,” he said.

He spent the summers exploring the banks of the Manasquan River, later learning to sail with his uncle and catching fish.

“That’s where I learned about life, about everything that I’m curious about,” he said.

On his senior yearbook page, Sharpless was nevertheless described as a “science whiz.” In a phone interview Wednesday, Friends’ Central classmate Tim Patterson recalled how everyone knew Sharpless was sharp. But he was not a showoff.

“He was just a regular guy,” said Patterson, a resident of Haverford. “He didn’t push anything in front of you saying he was brighter than the rest of us.”

During senior year, the pair played on the school’s undefeated football team, Sharpless as a lineman, Patterson said.

After graduating in 1959, Sharpless earned an undergraduate degree at Dartmouth College, in 1963, followed by a Ph.D. at Stanford University. He then joined the faculty at Massachusetts Institute of Technology, followed by another stint at Stanford, before going to Scripps in 1990.

Sharpless coined the phrase click chemistry in a 2001 paper, describing a class of carbon-based chemical reactions in which the pieces fit together as easily as Lego blocks, with few, if any, unwanted byproducts. He described his first example of such a reaction in a study the following year, working with Rostovtsev and others.

In that study, the scientists used copper as a catalyst — meaning the metal was used to turbocharge a reaction that joined two other substances, called azides and alkynes. That structure can in turn be used as a building block for modifying proteins and other molecules that are useful in drug discovery, Rostovtsev said.

“You can have other molecules hanging off those Lego pieces,” he said. “That’s what gives chemists the handles to dial in other properties.”

Sharpless was not available for interviews Wednesday, but in the past he has described how he stimulated his scientific thought process during long walks or runs along the Torrey Pines Mesa, on the Pacific Ocean, imagining how he could manipulate the three-dimensional shapes of molecules.

The Nobel comes with an award of 10 million Swedish kronor — about $910,000 — divided equally among Sharpless and his two co-winners.

The prizes in chemistry and other disciplines are to be given in a Dec. 10 ceremony in Stockholm.